A6 LYSOPHOSPHATIDYLCHOLINE (LPC) AND LYSOPHOSPHATIDIC ACID (LPA) INDUCE VISCERAL HYPERSENSITIVITY IN IRRITABLE BOWEL SYNDROME (IBS)
Bibliographic record
Abstract
Abstract Background Chronic abdominal pain is the key symptom in IBS. Gut microbiota produces a large variety of molecules that can regulate pain perception, including bioactive lipids. LPC and LPA are phospholipids, known to generate and maintain neurogenic pain in mammals, by directly activating multiple channels and G-protein coupled receptors on sensory neurons. LPC and LPA result from the conversion of phosphatidylcholine (PC), a major membrane-forming phospholipid in eucaryotes, as byproducts of inflammation. PC is also present in high concentration in eggs, meat and soybeans. It is unknown whether these two phospholipids play any role in chronic abdominal pain and whether they can be produced by the gut microbiota. Aims To investigate whether 1) LPC and LPA are increased in stool of IBS patients, and 2) whether microbiota from IBS patients can produce LPC and LPA and lead to visceral hypersensitivity. Methods Stool samples from 27 patients with IBS, collected both during periods of severe and minimal/no pain, were assessed for LPC and LPA levels by ELISA. Germ-free (GF) NIH Swiss and Swiss Webster mice (n=101) both sexes were colonized with fecal microbiota from IBS patients with either high or low fecal LPC and LPA levels, or microbiota from healthy controls. Mice were fed with control diet or diet enriched with PC diet (2g/kg of diet) for 5 weeks. Their visceral sensitivity was then assessed by measuring visceromotor responses to colorectal distension. The fecal samples were collected to measure the production of LPC and LPA Results The fecal concentrations of LPC and LPA were higher in IBS patients when experiencing severe abdominal pain, compared to periods of minimal or no pain. Mice colonized with fecal microbiota from IBS patients with high fecal LPC and/or LPA displayed visceral hypersensitivity compared to mice colonized with microbiota from healthy controls, or microbiota from patients with low fecal LPC and/or LPA levels. However, this increase in visceral sensitivity was only found in mice fed with diet enriched with PC. Furthermore, the increased pain responses to colorectal distension correlated with higher concentrations of fecal LPC and LPA. Conclusions Our data suggest that bacterial LPC and LPA is responsible for chronic abdominal pain in a subset of patients with IBS. Further studies are needed to identify the specific bacterial strains that produce these nociceptive phospholipids and precise mechanisms by which LPC and LPA induce visceral hypersensitivity. Funding Agencies CIHRThe W.Garfield Weston Foundation
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".